Chronic Obstructive Pulmonary
Disease (COPD)
• COPD is characterized by :
**Chronic airflow obstruction & accelerated
loss of lung function which is progressive & NOT
fully reversible.
** COPD is preventable & treatable but
NOT curable.
**In COPD, airway obstruction is fixed & irreversible
w/ different degrees of reversibility according to
patients.
• COPD is assoc. w/ abnormal response to noxious
chemicals or gases.
• Most common risk factor for COPD is SMOKING
• COPD pts. experience: -productive cough
-dyspnea
**See table2 p.920 for comparative table b/w
asthma & COPD
• General Goals of Management of COPD:
1) Prevent or slow disease progression.
2) Relieve symptoms.
3) Improve exercise tolerance.
4) Improve overall health status.
5) Prevent & treat complications.
6) Prevent & treat exacerbations.
7) Decrease mortality.
• 2 Major Forms of COPD:
1) Chronic Bronchitis (C.B.)
2) Emphysema
1) Chronic Bronchitis (C.B.):
Defined clinically as chronic excessive secretion into
bronchial tree occurring most days during a period of @
least 3 months /yr for @ least 2 consecutive yrs.
2) Emphysema:
Defined anatomically as abnormal permanent enlargement
of the alveoli distal to terminal bronchioles accompanied by
destruction of their walls without fibrosis.
• Both C.B.& emphysema are :
1) Indistinguishable.
2) Have different risk factors.
3) Have similar management strategies.
** Although Asthma & COPD are both characterized
by airflow obstruction, their pathophysiologic
features & response to treatment are different.
• Etiology:
*Smoking is major risk factor for COPD.
• About 80-90% of COPD pts. have a history of current or
past smoking although only 15-20% of smokers
develop COPD due to genetic variation.
• Other R.F. include:
1. Environmental factors(pollution&occupational)
2. Recurrent pulm. infections in childhood.
3. α₁ antitrypsin deficiency: Rare & inherited (<1% of
emphysema cases)
• Exacerbations of COPD typically have an
infectious etiology, either viral or bacterial.
• During an exacerbation, there is:
1) Increased S/S
2) Increased mucus production
3) Worsening of gas exchange
4) Worsening of airway obstruction assoc. w/ an
increased risk of resp. failure.
• Clinical Presentation & Diagnosis:
• Clinical assessment of COPD pts. includes:
1) Medical history
2) Physical examination
• Diagnosis of COPD is considered w/complaints of:
*Chronic cough
*Dyspnea
*Sputum production
* + History of risk factors
• Signs & Symptoms:
• Pathophysiologic changes progress over yrs. & clinical symptoms occur
later.
• By time pt. seeks med. help, disease is far advanced.
• Sig. overlap b/w clinical presentation of C.B. & Dyspnea.
Productive cough is assoc. more w/ C.B.
• Dyspnea is more assoc. w/ Emphysema.
• Obesity is assoc. w/ C.B. (Blue bloaters)
• Wt. loss is assoc. w/ Dyspnea (Pink puffers)
• Gold standard for COPD diagnosis is spirometry: FEV1/FVC < 70%
• When SABA is administered & spirometry is repeated in 15-30 min.:
-COPD is typically characterized by < 12% improvement in FEV1
(or <200ml in pts w/ very low lung volumes).
- A large increase in FEV1 is more consistent w/ asthma.
• COPD progression may develop acute &
chronic complications, i.e.:
1)Pulm. HTN
2)Cor Pulmonale & Rt. CHF ( Blue Bloaters )
3)Polycythemia
4)Hypoxemia & resp. acidosis
5)Emphysematous (Pink Puffers)
• An individualized approach to therapy should
be: 1) Appropriate
2) Based on the severity classification
3) Patient’s risk factors
• Important initial intervention: to reduce or
eliminate exposure to risk factors.
• Smoking cessation: the only treatment
strategy proven to slow the chronic
progressive loss of lung function.
• Approaches to Treatment:
• Pharmacotherapy:
• None of the currently available therapies is
shown to prevent or slow progressive loss of lung
function.
• 1⁰ role : symptomatic relief
• 1⁰ strategy: using bronchodilators.
• Response to meds. : Different among pts.
• Assessment of response & S/Es (table35.8 p.926)
• Reversibility of airflow limitation through spirometry
(FEV1) : Not shown in many pts.
• Dyspnea : Major debilitating symptoms for advanced
dz. pts.
• Inhaled route of adm.(MDI, DPI, Neb.):
-Pref. because > effective, faster onset & safer than
oral.
-All inhaled mechanisms are equally effective in
chronic management.
-MDI & DPI: > convenient
-Nebulizer: initial treatment in exacerbation.
*Bronchodilator combination used for additive
benefits & reduced S/Es.
1) Bronchodilaters:
A. Beta-2 Agonists:
-SABA
-LABA
B. Anticholinergics:
-SA Ach
-LA Ach
C. Methylxanthines
I. Bronchodilators:
A) Beta-2 Agonists:
Examples of SABA:
-Albuterol
-Pirbterol
-Terbutaline
*Albuterol:- Most commonly used inhaled SABA.
- < 5 min OA
-Relativ. short DA ( 4̴ hrs.w/chronic use)
*In COPD, SABA: -Relieves symptoms
-Improves exercise tolerance
-No sig. lung function improvement
Examples of LABA: ( DA 1̴ 2hrs)
-Formoterol (OA ̴ 5min., pk. ̴ 30min.)
-Salmeterol ( OA ̴ 15min., pk. ̴ 1-2 hrs.)
Difference NOT
important
clinically
*Sig. advantage of LABA over SABA
*Considered for those NOT controlled w/ SABA
• For more frequent or chronic symptoms, long acting
bronchodilators (LABA, LA Ach.) are more effective in:
1. Improving lung function
2. Improving exercise tolerance
3. Improving quality of life
4. Reducing frequency of exacerbations
B) Anticholinergics:
1) Short Acting:
Ipratropium Br.: (by inhalation)
* ≥ bronchodilation than SABA @usual doses.
*Little systemic absorption.
*OA within 15 min., DA 4-6 hrs.
*@ max. doses bronchodilation by beta-2 agonists maybe = to
that of ipratropium in COPD but S/Es are more common
w/SABA.
*Due to slower OA, SABA may be preferred for acute
bronchospasm w/ ipratropium used on scheduled basis.
*Given as 2 inhalations QID increased to 6 inh. if needed.
2) Long Acting:
Tiotropium:
*Once daily dosing regimen.
*Comparing Tiotropium w/Ipratropium in COPD:
1.Tiotrop. used QD, Ipratrop. used QID.
2. < Multiple exacerbations w/ Tiotrop.
3. Sig. longer time to 1st exacerbation w/Tiotrop.
4. For most outcomes, Tiotrop.> effective than
Ipratrop. but > expensive.
• Studies did NOT show significant clinical difference
between LABA & Tiotropium in COPD management.
• Short- acting bronchodilators (Albuterol +
Ipratropium) combination increase effectiveness & as
per treatment guidelines are commonly used in the
management of Mild-Mod. COPD.
• Limited data are available on the use of Long-Acting
Bronchodilators combination, however,
(LABA + Tiotropium) combinations are used for
severe COPD patients.
C) Methylxanthines:
• Theophylline is currently considered a 3rd- line
agent in the management of COPD due to the
availability of safer & more potent therapies
& its risk of toxicities.
• Issues to be considered with the use of Theoph.:
1) Different dosage forms &salts of theoph. are
available.(SR QD or BID are most appropriate)
2) Significant variability in bioavail. between different
products & patients.
3) Recommended therapeutic range for COPD 8-12ug/ml.
4) Smoking , other drugs, & disease factors interact w/
theoph. Careful monitoring of serum theoph. conc. is
important.
5) Sig. S/E profile involves: GI, CNS, CV.
• Summary of Bronchodilator Therapy:
1) Bronchodilators are the mainstay of therapy for chronic COPD
management.
2) Inhaled form preferred over systemic.
3) Short-acting agents are used initially.
4) If symptoms continue, LA agents are >effective & convenient:
Different trials showed long-acting bronchodilators (LABA &
LA Ach) provided > benefit in improving different outcome
measures than Short-Acting agents
(SABA & SA Ach).
5) Bronchodilator combinations are commonly used with added
benefit & reduced S/Es from higher doses of a single agent.
6) Oral theoph. Is an option reserved for those NOT responding
to inhaled regimens or refuse to use inhaled meds.
II. Corticosteroids:
• Did NOT result in dramatic response (unlike in
asthma) which may be due to neutrophilic
nature of COPD.
• Systemic corticosteroid should be avoided in
chronic COPD due to its lack of benefit &
serious toxicity.
• ICS has superior safety over systemic.
• Current Guidelines suggest:
Trial of ICS therapy warranted in patients:
1) whose FEV1 < 50%.
& 2) who experience frequent exacerbations.
*Newer ICS agents i.e.: -budesonide
-fluticasone
-mometasone
May have less of a risk of S/Es.
• Combination of LABA & ICS:
-For convenience & ease of use.
-Showed greatest FEV1 response w/ No
difference in the exacerbation rate.
*Mucolytic/Expectorant agents:
- Showed NO clinical benefit in COPD.
*Respiratory stimulants:
-Not recommended due to short-lived effect +
potential risk.
• α₁-Antitrypsin Replacement Therapy:
- Only used for the rare inherited form of
emphysema.
- Requires weekly or twice weekly infusions.
- Not indicated for other forms of emphysema.
• Non-pharmacologic Approaches:
1) Tobacco Cessation
2) Pulmonary Rehabilitation
3) Nutritional Therapy
4) Keeping Immunization Current
5) Supplemental O₂ Therapy
1) Tobacco Cessation:
* Difficult to achieve & maintain.
• The most important intervention in the
prevention & treatment of COPD.
• Slows the rate of loss of lung function
• Most important & beneficial intervention
• Associated w/ immediate & sustained health
benefit.
2) Pulmonary Rehabilitation:
a. Patient Education ( ̴Dz., technique,
adherence, self management skills).
b. Exercise Training.
c. Psychological Support & intervention
(for anxiety & depression).
d. Nutritional Therapy.
3) Nutritional therapy in COPD was shown to be
valuable in: 1. Relieving symptoms
2. Improving exercise tolerance
3. Improving overall health status
• Poor nutrition has sig. impact on COPD.
• Pulm. Rehab.:
1. Less beneficial in preventing complications &
exacerbations.
2. No effect in reducing mortality or slowing dz.
progression.
4) Keeping Immunization Current:
a. The inactivated IM Influenza virus vaccine
should be used because it has been shown
to reduce serious illness & death in COPD
pts.
b. Pneumococcal vaccine is recommended to
be given SQ or IM because it provides
prophylaxis against most common strains of
Strep. Pneumiae.
5) Supplemental O₂ Therapy: (Long-Term Therapy)
-Improves survival in COPD pts. w/ chronic hypoxemia.
-Benefit seen if:
- pO₂<55mmHg
or -pO₂<60mmHg w/ evidence of end- organ effect
of COPD, i.e.:*Cor pulmonale
*Polycythemia
*Cognitive impairment
• Greatest benefit shown in those who used O₂
for @ least 15hrs/d.
• Nasal Cannula: The most common &
convenient method of O₂
supplementation.
• ABGs & Pulse Oximetry: The 1⁰ methods for
determining O₂
saturation.
• Goal of Therapy: Maintain O₂ saturation ≥ 90%.
• Most are managed @ flow rates of 1-4L/min.
• Surgical Management:
• For those who can NOT be managed medically.
1. Bullectomy: -Removing bullea (large air spaces in
lungs)not participating in gas exchange
2. Lung Volume Reduction Surgery (LVRS):
-More common
-More comprehensive procedure
in removing non-functional
segments of lung tissue.
3. Lung Transplantation:-Used in advanced COPD
• Managing Exacerbations:
• Associated w/ increased morbidity & mortality.
• Acute worsening in patient’s baseline, i.e.:
-worsening dyspnea
-increased cough
-change in volume & appearance of sputum
beyond the day-to-day variations.
• Severity: Levels 1-3
-Level 1: Managed as outpatient (E.R.)
-Level 2: Requires hospitalization
-Level 3: Complicated by respiratory failure
• General Management:
1) Supplemental O₂ if warranted.
2) Intensification of bronchodilation therapy.
3) Systemic corticosteroid therapy.
4) Antibiotics in most cases.
5) Ventilatory support if respiratory failure is
present.
1) Level 1:
• Commonly treated w/ intensification of
bronchodilator therapy:
-Increase dose of SA bronchodilators
(comb. SABA + Ipratropium) by MDI or Neb.
-Less evidence to the role of LA
bronchodilators: Guidelines recommend
LA bronchodilators to be
continued or added if pt’s
condition warrants.
• Level 1 therapy involves use of Short Course of
Systemic Corticosteroid:
-improves lung function.
& -reduces relapse rate.
**Prednisone 0.5-1 mg/kg/d X 10-14 d
* Insufficient data on ICS use in COPD
exacerbation
• Antibiotics are commonly used in COPD exacerbations:
* S.Pneumoniae, M.Catarrhalis, H.Influenzae were found in pts.
w/ stable COPD or exacerbation representing either
colonization or infection.
*The presence of 2 of 3 of the following is an indicator for
antibiotic use:
1. Increased dyspnea
2. Increased sputum
3. Increased sputum purulance
**Traditional antibiotics are as effective as newer ones
** Duration of antibiotic therapy= 7-10 days
2) Level 2:
• Frequently treated as inpatients.
• Treatment approach similar to level 1.
• Oral antibiotics & corticosteroid if possible
(as effective as parenteral)
• Consider extended-spectrum antibiotics
esp. if Ps. Auroginosa is suspected.
3) Level 3:
• May require ventilatory support.
• Aggressive bronchodilator therapy.
• Corticosteroid therapy.
• Broad-spectrum antibiotics may be warranted
initially.
• Follow-up w/in 1 month of hospitalization.
* Theophylline oral or IV has minimum benefit in acute
exacerbations of COPD.
** Prophylactic Antibiotics to reduce exacerbations is
NOT proven effective & increases the risk of
resistance.
** Very Important Tables:
1) Table 35.11 p.935: General Principles for
Pharmacotherapy of COPD
2) Table 35.12 p. 936